Thermal plasmas and lasers have been widely used in medicine to cut tissues through heating. The effects of such thermal plasmas on tissues are non-selective and difficult to control because they occur primarily through transfer of intense heat. In contrast, non-thermal plasma does not produce heat, thus its effects are more selective. Although electrical discharges that generate non-thermal plasma have been known for a long time, their clinical potential has been largely ignored and until recently, applications have been confined to sterilization of inert surfaces or modulation of cell attachment. The exploitation of cold plasma for clinical applications requires the mechanistic understanding of the interaction of non-thermal plasma with living tissues.
US patent application 2010/0130911 describes a plasma source device which provides a reduced pressure in the ionization chamber. This device is adapted for the sterilization of wounds. Patent application WO2005/084569 discloses a disposable gas plasma tissue resurfacing instrument for skin treatment comprising an electromagnetically resonant focusing element. The aforementioned patent applications pertain to treating the tissues on the surface of wounds.
KR patent application 20140002357 discloses a food surface sterilization method using non-thermal plasma. The sterilization method of the present invention selects non-thermal plasma which is suitable for the food group and optimizes the treatment condition, so as to increases the sterilization effect to the microorganism on the surface of food materials or food, and to decompose the residual agricultural chemical components on the surface of the food materials or food. US patent application 2002175068 teaches decontamination of fluids or objects contaminated with chemical or biological agents using a distributed plasma reactor. In this publication, a corona discharge can be generated using very short high voltage pulses (pulsed discharge) produced by a Tesla coil. Another pulsed discharge embodiment incorporates a primary coil surrounding a chamber having a void filled with a plurality of secondary coils. In one embodiment the apparatus comprises a blanket-like structure that is useful for decontaminating a surfaces or decontaminating a fluid passing between spaced-apart bare electrodes. In another embodiment the bare electrodes define an internal treatment volume through which a contaminated fluid flows.
It has been shown that non-thermal plasma created by dielectric barrier discharge (DBD) has dose-dependent effects on mammalian cells in culture that range from increasing cell proliferation to inducing apoptosis. It has been further shown that these effects are primarily due to the formation of intracellular reactive oxygen species (ROS), which are known to cause DNA damage (S. Kalghatgi, C. Kelly, E. Cerchar, A. Fridman, G. Friedman, J. Azizkhan-Clifford, Effects of Non-Thermal Plasma on Mammalian Cells PLoS ONE, 21 Jan. 2011. 6(1)). US patent application 2010/0145253 relates to application of plasma to living tissue in vitro. Thus means and methods for inducing biological and/or biochemical effects on a whole subject, in vivo, using non thermal gas plasma treatment are still required.
The influence of plasma treatment on seed germination has been studied (I. Filatova et al. The effect of plasma treatment of seeds of some grain and legumes, on their sowing quality and productivity, Rom. Journ. Phys. Vol. 56, 139-143, 2011; S. Bozena et al, Influence of plasma treatment on wheat and oat germination, IEEE Transactions on plasma science, vol. 38, 2010). These studies describe an apparatus comprising a vacuum chamber, a rotary pump and a microwave resonator. The exposure time to the plasma treatment was for a period of several minutes to more than 40 min. Furthermore, the effects reported by these studies mainly relate to the seed coat surface and seed coat sterilization.
The publication of Park et al. (2012) Analysis of the biological effects of a non-thermal plasma on Saccharomyces cerevisiae, Journal of the Korean Physical Society Vol. 60 pp. 916-920 teaches the cellular and the molecular responses of eukaryotic yeast to a non-thermal plasma at atmospheric pressure. It was shown that when yeast cells are exposed to a DBD plasma, the number of surviving cells is reduced by more than 50%. It was further demonstrated in this publication that the protein profile of the yeast treated with the plasma exposure was affected by the plasma treatment, relative to control yeast.
Several publications teach the enhanced production of butanol by engineered Saccharomyces cerevisiae. Steen et al (2008) Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol, Microbial Cell Factories Vol. 7, pp. 36 discloses Saccharomyces cerevisiae engineered with an n-butanol biosynthetic pathway showing an improved production of n-butanol by ten-fold relative to a control. Si et al (2014) Utilizing an endogenous pathway for 1-butanol production in Saccharomyces cerevisiae, Metabolic Engineering Vol. 22 pp. 60-68 reports the improved accumulation of butanol of engineered endogenous 1-butanol pathway Saccharomyces cerevisiae. Swidah et al. (2015) Butanol production in S. cerevisiae via a synthetic ABE pathway is enhanced by specific metabolic engineering and butanol resistance, Biotechnology for Biofuels, Vol. 8 pp. 97 reports that appreciable levels of n-butanol can be achieved in S. cerevisiae by transplanting an n-butanol synthesis pathway from Clostridial sp. into the genome of S. cerevisiae strain. Sakuragi et al. (2015) Enhanced butanol production by eukaryotic Saccharomyces cerevisiae engineered to contain an improved pathway Bioscience Biotechnology and Biochemistry Vol. 79, pp. 314-320 teaches the introduction of the butanol production pathway of Clostridium acetobutylicum into yeast Saccharomyces cerevisiae. It was reported that the elimination of glycerol production pathway in the yeast contributed to the enhancement of 1-butanol production. In addition, by the use of trans-enoyl-CoA reductase in the engineered pathway, 1-butanol production was markedly enhanced.
There is therefore a long felt and unmet need to provide systems and methods for inducing biological and or biochemical effects on a subject, using efficacious non thermal gas plasma treatments and protocols.